罗红霉素对LPS诱导的肺泡巨噬细胞NF-κB活化及对TNF-α,IL-10释放的影响  

Effect of roxithromycin on activity of NF-κB and expression of TNF-α and IL-10 in pulmonary alveolar macrophage

作　　者：王晓斌[1] 贾斌[1] 赵澎涛[1] 董明清[1] 张莉莉[1] 刘毅[1] 林树新[1] 李志超[1] 

机构地区：[1]第四军医大学基础部病理生理学教研室,陕西西安710033

出　　处：《第四军医大学学报》2005年第5期450-453,共4页Journal of the Fourth Military Medical University

摘　　要：目的:探讨罗红霉素(RM)对内毒素(LPS)诱导下肺泡巨噬细胞(PAM)核因子-κB(NF-κB)活化及对肿瘤坏死因子-α(TNF-α)和IL-10表达的调节作用. 方法:收集大鼠支气管肺泡灌洗液中PAM进行培养,分为正常对照组、模型组和RM治疗组. 用凝胶电泳迁移率改变分析(EMSA)法和放射免疫法分别测定各组核提取物中NF-κB活性和细胞培养上清中TNF-α,IL-10含量. 结果:模型组NF-κB活性明显高于正常对照组,用RM干预后NF-κB活性高于正常对照组(P<0.05),但比模型组低(P<0.05). LPS刺激1~4 h内TNF-α含量高于正常对照组;RM(20 mg/L) 能够抑制培养上清液中TNF-α的升高(P<0.05). NF-κB活性与TNF-α浓度有相关性(r=0.684,P<0.01). LPS刺激在观察早期IL-10高于正常对照组(P<0.05),使用RM干预后IL-10无明显变化(P>0.05). 正常对照组与治疗组TNF-α/IL-10比值在观察期间无明显上升和下降,模型组TNF-α/IL-10比值变化明显. 结论:RM可能通过PAM NF-κB活化的抑制,减少了TNF-α的释放,调节TNF-α/IL-10的比例,对LPS诱导的急性肺损伤模型有保护作用.AIM: To evaluate the effects of roxithromycin on the activation of nuclear factor-κB (NF-κB) and the expression of tumor necrosis factor-α(TNF-α) and Interleukin-10 (IL-10) in pulmonary alveolar macrophages (PAM) induced by lipopolysaccharide (LPS). METHODS: PAM were collected from bronchoalveolar lavage fluid and cultured, and then they were divided into 3 groups: normal control group, model group (LPS 10 mg/L) and roxithromycin treatment group (roxithromycin 20 mg/L and LPS 10 mg/L). The activity of NF-κB and the concentration of TNF-α and IL-10 in the supernatant were measured by electrophoretic mobility shift assay (EMSA) and radioimmunoassay (RIA) respectively. RESULTS: The activity of NF-κB in model group was higher than that in normal group. After roxithromycin treatment, the NF-κB activity was higher than that in normal control group(P<0.05), but lower than that in model group(P<0.05). The concentration of TNF-α in model group after exposure to LPS was higher than that in normal group. Compared with that in model group, TNF-α in roxithromycin treatment group decreased significantly (P< 0.05). The correlation between the activity of NF-κB and the concentration of TNF-α was significant (r=0.684, P<0.01). In model group, the concentration of IL-10 augmented compared with that in normal group (P<0.05) and there was no effect on expression of IL-10 after roxithromycin treatment (P>0.05). The ratio of TNF-α and IL-10 in normal group and roxithromycin treatment group remained constant, while the ratio in model group changed with the culture prolongation. CONCLUSION: Based on these results, we conclude that when PAM is stimulated by LPS, NF-κB in the PAM will be activated, which can lead to transcription and expression of many inflammatory cytokine such as TNF-α and anti-inflammatory cytokine such as IL-10. The equilibrium of inflammation and anti-inflammation will be broken. Roxithromycin can regualte the ratio of TNF-α and IL-10 and decrease the concentration of TNF-α by inhibiting the a

关 键 词：肺泡巨噬细胞 核因子-ΚB 肿瘤坏死因子-α 白细胞介素-10 罗红霉素 

分 类 号：R363.21[医药卫生—病理学]